Vhl is a tumor suppressor gene localized on chromosome 3p2526. Clinical hallmarks of vhl disease include the development of retinal and central nervous system cns hemangioblastomas bl. Approximately 6575% of patients with vhl as a component of multivisceral tumors have some form of pancreatic lesions cystic and solid tumors 2. Peripheral retinal nonperfusion using widefield imaging. This disorder is not rare about one in 36 000 livebirths and is inherited as a highly penetrant autosomal dominant trait ie, with a high individual risk of disease. Vhl is caused by a germline mutation in the vhl gene and has an incidence of one in 36,000 live births, with a 90% penetrance by the age of 65 1,2. A multidisciplinary team approach is important in screening. Case discussion spinal hemangioblastomas are less common than those located in the cerebellar hemispheres accounting for 80% of such tumors. It is caused by a flaw in one gene, the vhl gene, which regulates cell growth causing patients to battle a series of tumors throughout their life. New approach, new scope, new guidelines created date.
More recently, vhl has also been shown to harbor mutations in mesothelioma and small cell lung carcinoma. Genetic, clinical, and imaging features radiology march 146. Also, an early detection allows the patients survival and quality of life. Patients undergo an annual clinical screening program including. Stop adrenalparaganglioma imaging if no lesions ever developed. This is the only gene currently known to cause vhl. Until a cure is found, surveillance is a patients strongest defense to prevent severe vhl complications. Wholebody mri in oncology and vhl disease practiceupdate. In this case, we describe the wide magnetic resonance imaging mri spectrum in a single patient who had multi organ involvement. Stop or reduce kidney imaging stop cns mri if no lesions ever. Vhl syndrome is inherited in an autosomal dominant manner and is caused by a change that affects the vhl gene, a tumorsuppressor gene, on chromosome 3. Affected patients develop central nervous system hemangioblastomas and abdominal tumors, among other lesions. S and 200,000 cases worldwide and 20% of patients are firstin. The utility of 68galliumdotatate petct in the detection.
The product of the vhl gene is an e3 ubiquitin ligase that regulates the stability of the hypoxiainducible factor alpha subunits. Its course is accompanied by the development of multiple neoplasms with the following tumours diagnosed most. Tumors in vhl include hemangioblastomas, which are blood vessel tumors of the brain, spinal cord, and eye. Stop pancreatic imaging if no lesions ever developed. The presence of more than one hemangioblastoma in the central nervous system is the most characteristic feature of this phakomatosis.
Hemangioblastomas can also occur in the lightsensitive tissue that lines the back of. Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination ataxia. Sagittal magnetic resonance imaging mri of the cervical spine shows 4. The most common pathological lesions are hemangioblastomas of the central nervous system, retinal angiomas, renal clear cell carcinomas, and pheochromocytomas. These abnormal growths can further develop into tumors and cysts. These tumors may be benign or malignant but can often cause other problems depending on where they are located in the body. Radiologic imaging is very important for the early diagnosis and treatment of asymptomatic patients. Describe the prevalence, genetics, clinical manifestations, and management of vhl disease. A germline mutation of this gene is the basis of familial inheritance of vhl syndrome.
Sagittal vertebral angiogram of the same patient as in the previous 3 images shows a hypervascular intramural nodule open arrow that demonstrates a prolonged and intense enhancement with a surrounding avascular area, representing the cyst surrounding the mural nodule solid arrows. The endolymphatic sac tumors can diminish hearing, which is a key symptom of vhl syndrome. Inheritance is autosomal dominant with high penetrance and variable expression, and the condition is associated with inactivation of a tumor suppression gene located on chro. Early recognition and treatment of specific manifestations of vhl can substantially decrease. It is characterized by visceral cysts and benign tumors with potential for subsequent malignant transformation. The spectrum of clinical manifestations of the disease is broad and includes retinal and central nervous system hemangioblastomas, endolymphatic sac tumors. Vhl is caused by a germline mutation in the vhl gene and has an incidence of one in 36,000 live births, with a 90% penetrance by the age of 65 1, 2. The vhl alliance is a major resource for vhl diagnosis, screening and treatment. She underwent widefield fluorescein angiography, which showed hyperfluorescence localized to the hemangioblastoma surrounded by peripheral retinal nonperfusion in the same quadrant. These tumors can be either benign noncancerous and malignant cancerous.
They can grow in your brain and spinal cord, kidneys, pancreas, adrenal glands, and reproductive tract. Background vhl disease is a rare autosomal dominant inherited syndrome with high penetrance and variable expression, which involves inactivation of tumour suppressor gene on chromosome 3p25. A focused 35minute whole body mri screening protocol for. The hemangioblastomas in the retina can cause vision loss and may be the initial sign of vhl syndrome. Contrastenhanced ultrasound as a screening tool for. Enhancing lesion of the left eye globe likely represent retinal hemangioblastoma. A focused 35minute whole body mri screening protocol for patients. An autosomal dominant disorder, caused by a defective tumor suppressor gene, vhl, at chromosome 3 and characterized by the occurrence of various tumors in different organs. Vhla suggested active surveillance guidelines vhl alliance. Patients undergo an annual clinical screening program including separate magnetic resonance imaging mri of the brain, whole spine and abdomen. A small nodular enhancing lesion, with mild surrounding vasogenic edema, is noted in the right cerebellar hemisphere. Small solid lateral cerebellar hemangioblastoma, in a. Vhl disease is an inherited disorder that causes tumors and cysts to grow in certain areas of the body, including the central nervous system including the brainstem, cerebellum, and spinal cord, retina, endolymphatic sac in the ear, adrenal glands, pancreas, kidneys, epididymis.
Recognize the imaging appearances of various manifestations of vhl disease. Central nervous system and retina tumors called hemangioblastomas. Vhl mutations are known to cause a predictable series of events leading cancer in the kidneys and a few selected other tissues. The purpose of this study is to determine if contrastenhanced ultrasound can detect abnormal features of kidney lesions in patients with vonhippel lindau with the same accuracy as conventional ultrasound and contrastenhanced magnetic resonance imaging mri. Vhl disease effects 1 in 36,000 people 10,000 cases in the u. Small solid lateral cerebellar hemangioblastoma, in a patient. Vhl is caused by a mutation in the gene that controls cell growth, located on your third chromosome. Value of optical coherence tomography angiography imaging. Tumors may be either noncancerous or cancerous and most frequently appear during young adulthood. Slowgrowing hemgioblastomas benign tumors with many blood vessels may develop in the brain, spinal cord, the retinas of the eyes, and near the inner ear. Treatment for vhl disease manifestations was recorded up to 12 mo after. A brain tumor, left unchecked, can cause an aneurysm. Statistical analysis was performed using r software r core team, 2015, version 3.
The program allows patients to be seen by specialists familiar with vhl disease. Software and database for the analysis of mutations in the. They are also at an increased risk of developing a type of kidney cancer called clear cell renal cell carcinoma and a type of pancreatic cancer called a pancreatic neuroendocrine tumor. Due to its high recurrence rate and complex and diverse clinical manifestations, vhl is prone to being either misdiagnosed or missed entirely. Therefore, patients with vhl syndrome have a poor prognosis.
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